Synthesis of tetrazoles catalyzed by a new and recoverable nanocatalyst of cobalt on modified boehmite NPs with 1,3-bis(pyridin-3-ylmethyl)thiourea

In the first part of this work, boehmite nanoparticles (BNPs) were synthesized from aqueous solutions of NaOH and Al(NO3)3·9H2O. Then, the BNPs surface was modified using 3-choloropropyltrimtoxysilane (CPTMS) and then 1,3-bis(pyridin-3-ylmethyl)thiourea ((PYT)2) was anchored on the surface of the modified BNPs (CPTMS@BNPs). In the final step, a complex of cobalt was stabilized on its surface (Co-(PYT)2@BNPs). The final obtained nanoparticles were characterized by FT-IR spectra, TGA analysis, SEM imaging, WDX analysis, EDS analysis, and XRD patterns. In the second part, Co-(PYT)2@BNPs were used as a highly efficient, retrievable, stable, and organic–inorganic hybrid nanocatalyst for the formation of organic heterocyclic compounds such as tetrazole derivatives. Co-(PYT)2@BNPs as a novel nanocatalyst are stable and have a heterogeneous nature; therefore, they can be recovered and reused again for several consecutive runs without any re-activation.


Introduction
In recent years, boehmite nanoparticles (BNPs) have attracted interest from both practical and fundamental viewpoints. 1,2 In fact, boehmite is aluminum oxyhydroxide (g-AlOOH) and it is the most stable phase of alumina aer gibbsite. [3][4][5][6] Boehmite consists of double sheets of oxygen octahedron with Al-atoms at their centers. [7][8][9][10] The boehmite sheets themselves are composed of octahedral chains with a cubic orthorhombic unit cell. 2,11 Also, BNPs are very stable and they are not moisture or air sensitive. 12,13 Therefore, BNPs can synthesized in aqueous media without inert atmosphere by available materials such as inexpensive aluminum salts. 14 The physical and chemical properties of boehmite are strongly dependent on the experimental condition of its synthesis. 13 For example, BNPs were synthesized by different methods such as hydrolysis of aluminum salts, 2 precipitation in an aqueous solution from aluminum salt solutions, 15 hydrothermal procedures, 2 solid state decomposition of gibbsite, 16 sol-gel procedures, 17 and solvothermal procedures. 2 Boehmite contains high aggregation of hydroxyl groups on its surface, that supply suable places for modify of its surface with other functional groups such as electrophilic or nucleophilic sites which are enable to immobilization of suitable ligands or metal complexes. [18][19][20][21][22] Therefore BNPs can be used as an excellent support for fabrication of wide range of heterogeneous catalysts. 2 BNPs were utilized as support for stabilization of acidic, 23 basic, 24 metallic catalysts 25,26 and organo-or ionic 22 supported catalysts. More addition, boehmite nanoparticle have several unique attributes such as good surface area, easy availability, non-toxicity, chemical resistance, mechanical strength, thermal stability, good conductivity, high hardness, low cost, excellent biocompatibility, high abrasive and corrosion resistance. 1,2,22 However, BNPs are also have some disadvantages, such as impurities content (e.g. nitrate ions) that led to lower their crystallinity. This impurities concentration may affect properties of the surface property and pore structure of boehmite. In the other hand, BNPs may converts into a g-Al 2 O 3 in the high temperatures, but this cannot effect on the catalysis application of BNPs in organic reactions. Because organic reactions take place at temperatures lower than the BNPs phase change. Therefore, Boehmite nanomaterials have also attracted attention in absorbent, 27 coatings, 28 ame retardant, 29 optical material, 30 ceramics, 31 vaccine adjuvants, 32 cosmetic products, 2,33 pillared clays and sweep-occulation for fresh water treatment. 13 Consequently, we investigated a new complex of cobalt with 1,3bis(pyridin-3-ylmethyl)thiourea on boehmite nanoparticle (Co-(PYT) 2 @BNPs) as a reusable nanocatalyst in the synthesis of tetrazole derivatives. Because tetrazole compounds are an important group of medicinal and organic compounds which possess many uses in several elds such as coordination chemistry, synthetic organic chemistry, drugs, medicinal chemistry as surrogates for carboxylic acids, the photographic industry, catalysis technology, and organometallic chemistry as effective stabilizers of metallopeptide structures. [34][35][36][37][38][39][40][41] 2 Experimental

Materials and instruments
Solvents and chemical materials in this project bought from Iranian companies, Aldrich, Merck or Fluka and used sans any purication.
The particle morphology and particle diameters of synthesized catalyst studied via FESEM-TESCAN MIRA III Scanning-Electron-Microscope (SEM) from Czechia. In addition, FESEM-TESCAN MIRA III used for type, content and number of elements (via WDX and SEM-EDS analysis) of the nanocatalyst. XRD diffraction of the nanocatalyst recorded by a PW1730 device madding Philips Company of Netherlands. IR spectra recorded using KBr pills in a VRTEX 70 model Bruker IR spectrometer. TGA diagram of the nanocatalyst recorded by a SDT Q600 V20.9 Build 20 Thermal Analysis device under air atmosphere in the temperature range of 30-800°C. NMR spectra of the tetrazoles registered via Bruker-DRX-400 spectrometer.

Synthesis of 1,3-bis(pyridin-3-ylmethyl)thiourea ((PYT) 2 ) ligand (3)
In a round-bottomed ask, 3-(aminomethyl)pyridine (1, 10 mmol) added to CS 2 (5 mmol) in H 2 O and stirred at room temperature for 7 h (Scheme 1). The reaction progress consecutively checked by TLC (EtOAc: n-hexane, 1 : 2). Since this reaction is exothermic, the temperature increases during the reaction and so this temperature is sufficient for release H 2 S (conrmed by smell and blackening of lead acetate paper). Aer performance of the reaction, the water-insoluble product ltered, and then recrystallized from hot water and ethanol (1 : The structure of (PYT) 2 ligand was characterized by 1

Synthesis of the catalyst
50 mL of aqueous solution of sodium hydroxide (6.490 g) was added to 30 mL of aqueous solution of aluminum nitrate (20 g) as drop to drop under vigorous stirring. The resulting milky mixture was transferred in the ultrasonic bath (for 3 h at room temperature). The resulted BNPs was ltered and washed by distilled water. The obtained BNPs were kept in the oven at 220°C for 4 h. Then, BNPs were modied by (3-chloropropyl)triethoxysilane (CPTMS) to preparation of CPTMS@BNPs. The CPTMS@BNPs formed matching to reported method in literature. 41,42 As reported, the BNPs (1.5 g) dispersed in normal hexane, and then CPTMS (2 mL) injected and the mixture stirred for 24 h under reux conditions that the modied BNPs by CPTMS (CPTMS@BNPs) were produced. The prepared CPTMS@BNPs were ltered, washed by ethanol (EtOH) and dried at room temperature. In order to immobilization of (PYT) 2 ligand (3) on CPTMS@BNPs, 1 g of CPTMS@BNPs reuxed with (PYT) 2 in toluene for 40 h. Aer then, obtained (PYT) 2 @BNPs isolated via ltration, washed by DMSO and EtOH, aerward dried at 60°C. Finally, (PYT) 2 @BNPs (1 g) was dispersed in EtOH, and then Co(NO 3 ) 2 $6H 2 O injected to the obtained mixture and then stirred for 24 h under reux conditions. The resulting catalyst (Co-(PYT) 2 @BNPs) ltered, washed and dried at 60°C (Scheme 2).
The obtained results from energy-dispersive X-ray spectroscopy (EDS) analysis of Co-(PYT) 2 @BNPs are summarized in Fig. 2. As shown, Co-(PYT) 2 @BNPs is organize from aluminum, oxygen, silicon, nitrogen, carbon, sulfur and cobalt elements. As accepted, the intensity peaks of Al and O elements is sharped than other elements which are formed skeleton of BNPs. Also, the presence of Si, C, N, S and Co elements indicate the successful stabilization of the cobalt complex on BNPs. Also, wavelength dispersive X-ray spectroscopy (WDX) analysis (Fig. 3) illustrate homogeneous distribution of aluminum, oxygen, silicon, nitrogen, carbon,  TGA analysis can used to determine amount of organic and inorganic content in an organic-inorganic composite samples and also can employed to calculate the thermal stability of materials. Therefore, TGA analysis of Co-(PYT) 2 @BNPs was performed from 25°C to 800°C within increasing temperature rate of 10°C min −1 under air atmosphere (Fig. 4). In TGA diagram of Co-(PYT) 2 @BNPs, a small weight losses (8% of weight) up to 150°C is corresponded to the evaporation of solvents. 43 As shown, any weight loss was not indicate up to 250°C except evaporation of solvents which showed excellent thermal stability of Co-(PYT) 2 @BNPs. Therefore Co-(PYT) 2 @-BNPs can be used as catalyst under hard conditions in wide range of organic reactions. TGA analysis of Co-(PYT) 2 @BNPs illustrated a considerable mass loss (35% of weight) between 250-650°C which due to the decomposition of immobilized organic layers on the surface of modied BNPs. 44 X-ray diffraction (XRD) pattern of Co-(PYT) 2 @BNPs is obtained with Cu Ka radiation (l = 0.154 nm). As shown in  (2 2 0), 54.19°(1 4 1) and 63.14°(5 0 3) which can be related to Cobalt(II) species. 33 The FT-IR spectrum of CPTMS@BNPs, (b) (PYT) 2 @BNPs, and (c) Co-(PYT) 2 @BNPs shown in Fig. 6. Bands vibration at low wavenumbers <750 cm −1 in the FT-IR spectra related to the vibrations of the Al-O bonds. 4 O-H and N-H bands appeared above 3000 cm −1 in the FT-IR spectra. 46 In addition, the stretching vibrations of Si-O identied in region 805 cm −1 and 1075 cm −1 of FT-IR spectra. 41,47 In addition, stretching vibrations of the C]N groups have appeared in the 1635 cm −1 region. 4,48

Catalytic studying of the catalyst
Aer characterization of Co-(PYT) 2 @BNPs, it was used as efficient, recyclable and biocompatible nanocatalyst in the synthesis of tetrazole heterocyclic compounds. The best reaction conditions obtained through [3 + 2] cycloaddition of NaN 3 and benzonitrile as model reaction ( Table 1). The model reaction did not taken place in the absent of Co-(PYT) 2 @BNPs nanocatalyst ( Table 1, entry 1). While, the presentence of Co-(PYT) 2 @BNPs is required for the synthesis of 5-substituted 1Htetrazole heterocyclic compounds. As expected, the model reaction occurs with the addition of catalyst and it faster proceeded by increasing in amount of Co-(PYT) 2 @BNPs catalyst. As shown, the model reaction completed within acceptable time when the amount of catalyst increased up to 50 mg (Table 1, entry 3). Among of several solvents (such as H 2 O, DMSO and PEG-400) which are examined, PEG-400 was provided the best results in term of reaction time and isolated yield of the pure product (Table 1, entry 3). Also, the effect of equivalent amount of NaN 3 to benzonitrile and temperature on the model reaction was studied, which the best results were obtained with 1.4 mmol of NaN 3 per 1 mmol of benzonitrile at 120°C (Table 1, entry 3).
The scope of catalytic application of Co-(PYT) 2 @BNPs nanocatalyst was extended in the [3 + 2] cycloaddition of NaN 3 and other benzonitrile derivatives ( Table 2). In this regard, several benzonitrile compounds with an electron-withdrawing or electron-donating groups on para-meta-or ortho-position of aromatic ring were examined under optimized reaction conditions in hand. As shown in Table 2, all corresponding heterocyclic tetrazoles were produced in good yields. Also, phthalonitrile was employed as nitrile substrate which has two similar cyano groups on 1,2 position of its aromatic ring (Table 2, entry 4). As shown in Table 2 (entry 4), this methodology was provided only monoaddition which may be related to steric hindrance or selectivity of this catalyst. Also [1,1 ′ -biphenyl]-4carbonitrile (4-phenyl benzonitrile) was synthesized based on recently reported literature 49 and it was investigated in the [3 + 2] cycloaddition reaction with NaN 3 ( Table 2, entry 11).
Based on reported authentic methodologies about synthesis of tetrazoles in the presence of immobilized transition metal catalysts, 46,54 a mechanism cycle for the synthesis of tetrazoles in the presence of Co-(PYT) 2 @BNPs catalyst offered in Scheme 4.

Reusability of the catalyst
As mentioned, Co-(PYT) 2 @BNPs catalyst is stable and it has heterogeneity nature. Therefore the reusability and   retrievability of Co-(PYT) 2 @BNPs nanocatalyst were investigated in the [3 + 2] cycloaddition of benzonitrile and NaN 3 for the synthesis of 5-phenyl-1H-tetrazole. As shown in Fig. 7, Co-(PYT) 2 @BNPs catalyst can be recovered and reused up to 6 runs without any further activation.

Comparison of the catalyst
The efficiency and advantages of Co-(PYT) 2 @BNPs catalyst than previous reported catalysts were compared in the [3 + 2] cycloaddition of benzonitrile with sodium azide in the presence of Co-(PYT) 2 @BNPs and previous catalysts ( Table 3). As shown, Co-(PYT) 2 @BNPs catalyst afford 98% of 5-phenyl-1Htetrazole product in 2 h which is better than previous reported catalysts in terms of time and yields. Also, some of previous catalysts have several disadvantages, limitations or drawbacks such as low yield of the products, long reaction times, expensive catalysts, non-environmental conditions, non or difficult separation of the catalysts and utilize hazard solvents. While, in this work, the synthesis of tetrazoles was introduced in the presence of Co-(PYT) 2 @BNPs as reusable catalyst in green solvent such as PEG, in short reaction time with acceptable yield.

Conflicts of interest
There are no conicts to declare.